The development and regeneration of peripheral sensory receptors involve dynamic biological processes in which progenitor cells ultimately form mature, functional receptors capable of transducing environmental stimuli. Such processes include induction, proliferation and differentiation, migration to the proper destinations, structural and functional maturation, maintenance of the cell cycle, and connections with the proper neural units. While these processes-are shared among sensory systems, important characteristics are unique to each Through a coordinated study of the commonalities and differences among the developing and regenerating systems, it will be possible to provide organizing principles that allow an understanding of peripheral sensory cell development and of sensory cell regeneration in response to injury. Thus, the long term goal of this Program Project Grant (PPG) is to examine common and unique processes during development and regeneration of sensory receptor cells in related sensory systems. Specifically, we will study olfactory, auditory, and gustatory receptor cell development and regeneration. The PPG is divided into three main, integrated projects that exploit the expertise and collaborative efforts of the investigators affiliated with the Program. In Project 1 the early embryonic induction of olfactory- and auditory-related structures will be studied. Projects 2 and 3 involve studies of the functional and morphological regeneration of mammalian auditory hair cells and gustatory receptor cells, respectively, and the role of the immune system in the regeneration of these sensory receptors. While clear commonalities exist among projects that share the same sensory system (e.g., auditory system) and the same experimental focus (e.g., development or regeneration), significant scientific and technical overlap is present among all projects. Therefore, experiments detailed in this proposal collectively form a program of study that is multidisciplinary in nature and ideally suited to investigate fundamental and timely issues common to peripheral sensory system development and regeneration.